| First Author | Ramakrishnan P | Year | 2016 |
| Journal | Diabetes | Volume | 65 |
| Issue | 8 | Pages | 2367-79 |
| PubMed ID | 27217485 | Mgi Jnum | J:249526 |
| Mgi Id | MGI:5922484 | Doi | 10.2337/db15-1607 |
| Citation | Ramakrishnan P, et al. (2016) Deficiency of Nuclear Factor-kappaB c-Rel Accelerates the Development of Autoimmune Diabetes in NOD Mice. Diabetes 65(8):2367-79 |
| abstractText | The nuclear factor-kappaB protein c-Rel plays a critical role in controlling autoimmunity. c-Rel-deficient mice are resistant to streptozotocin-induced diabetes, a drug-induced model of autoimmune diabetes. We generated c-Rel-deficient NOD mice to examine the role of c-Rel in the development of spontaneous autoimmune diabetes. We found that both CD4(+) and CD8(+) T cells from c-Rel-deficient NOD mice showed significantly decreased T-cell receptor-induced IL-2, IFN-gamma, and GM-CSF expression. Despite compromised T-cell function, c-Rel deficiency dramatically accelerated insulitis and hyperglycemia in NOD mice along with a substantial reduction in T-regulatory (Treg) cell numbers. Supplementation of isogenic c-Rel-competent Treg cells from prediabetic NOD mice reversed the accelerated diabetes development in c-Rel-deficient NOD mice. The results suggest that c-Rel-dependent Treg cell function is critical in suppressing early-onset autoimmune diabetogenesis in NOD mice. This study provides a novel natural system to study autoimmune diabetes pathogenesis and reveals a previously unknown c-Rel-dependent mechanistic difference between chemically induced and spontaneous diabetogenesis. The study also reveals a unique protective role of c-Rel in autoimmune diabetes, which is distinct from other T-cell-dependent autoimmune diseases such as arthritis and experimental autoimmune encephalomyelitis, where c-Rel promotes autoimmunity. |
